The long term objective of this proposal is to learn whether humoral mediators can influence or regulate intraocular pressure in normal and/or glaucomatous eyes. Evidence from clinical and laboratory sources indicates that intraocular pressure can vary in a circadian rhythm, fall in pregnancy, and fall in response to agents administered systemically that stimulate the production of cyclic AMP in ciliary epithelia, the tissue secreting aqueous humor. The specific aim of this research is to follow up our observation that certain glycoprotein hormones, in concentrations very similar to circulating levels of hormones found in vivo can reduce intraocular pressure. Studies will be initiated with HCG. The physiologic and cellular site of action will be determined and the chemical mechanism for the reduction of intraocular pressure be determined. Additional information from other glycoproteins and analogs of these and of HCG will be used to analyze the site of the response and its biochemical mechanisms. This proposal is consistent with the program base of the N.E.I. national plan for vision research of the glaucoma panel in its study of 1) cellular mechanisms of drug action to alter rate of inflow of aqueous humor, 2) the physiology and pathophysiology of aqueous humor inflow in hypotony, and 3) the cell biology of tissues involved in aqueous humor formation. The proposal to investigate endogenous neural and humoral regulating mechanisms is one of the N.E.I. glaucoma panels program development priorities.